What We're Reading
Cancer Immunol Res January 1 2021 9 (1) 1-1;
Macrophage polarization state, rather than overall density, in the colorectal cancer microenvironment is associated with cancer-specific survival independent of potential confounding factors, with M1-like and M2-like macrophage phenotypes exhibiting distinct prognostic roles.
A defect in ADH1-mediated retinoic acid synthesis contributes to the accumulation of polymorphonuclear (PMN)-MDSCs in colorectal cancer. The data highlight how restoring retinoic acid signaling could abrogate the generation of PMN-MDSCs and improve antitumor responses.
A genome-wide CRISPR screen was developed to understand cancer cell–derived resistance mechanisms to CD3-bispecific antibodies. The screen identifies IFNγ signaling being pivotal for responsiveness to CD3 bispecifics, and deficiency in core fucosylation as causing resistance to the therapeutic flotetuzumab.
The generation of a CD40-specific Vγ9Vδ2 T-cell engager, which abrogates prosurvival CD40 signaling, is described. This bispecific antibody unleashes Vγ9Vδ2 T cell–mediated responses against both leukemia and multiple myeloma in vitro and in vivo.
CD28 mutations enhance CAR T-cell function by reducing expression of transcription factors such as NFAT and NUR77, which in turn reduce expression of exhaustion-related genes. These data highlight considerations for CAR design that could improve antitumor responses.
In the clinic, CD19-CAR T cells are administered IV and are not used specifically to treat CNS lymphoma. The authors show a single ICV infusion of CD19-CAR T cells completely eradicates both CNS and systemic lymphoma in mice.
Activin A and TGFβ can shape the breast cancer tumor microenvironment after radiotherapy. Dual blockade of activin A and TGFβ reverses radiotherapy-induced Treg increases and boosts antitumor responses, highlighting potential targetable factors for breast cancer treatment.
Inaccurate TCR diversity estimates from RNA sequencing data have made the relationship between diversity and immunotherapy responses unclear. Improved estimation of diversity uncovers the association between diversity and responses of melanoma patients treated with PD-1 inhibition.
Silencing of the ST3GAL1 glycosyltransferase in breast cancer cells reduces O-sialylation of CD55, enhancing C3 deposition and susceptibility to complement- and antibody-dependent cytotoxicity. These findings suggest ST3GAL1 inhibition could be a strategy to block breast cancer immune evasion.